Gastrodin Nano-liposomes And Nano-microspheres

Gastrodia elata BI is one of rare medicine herb in china, which is a drying tuber of orchidaceous plant. It was widely used in dizzy, headache, limb numbness, half paralyzed, children convulsion and so on. The modern pharmacology research has proved: Gastrodia plays a great part on curing calm, anti-convulsion, anti-pain, antiphlogistic, anti-senescence, improving memory and has good effect on curing cardio Cerebrovascular disease with very light toxicity. These properties have attracted people's attentions. Presently, domestic research mainly focus on extracting, separating and determination gaetrodine. Little research can be seen on its dosage form. Consequently, the gastrodine pharmaceutical manufacturing technology of newly dosage form was emphasized in this paper, which expecting to provide basic evidence for development raw Gastrodia dosage form. In addition, a kind of simple, rapid determination gaetrodine method was constituted.The main task of this paper including a series of contents below: established the simple, rapid method to determine the gastrodine of gaxtraodia tuber; This method is confirmed by HPLC which is widely used. On this basis, the gastrodine's extraction technology was optimized; the "Thin-film evaporation"method was used in the preparation of gastrodine nano-liposome , and the multi-indicator quality characterization to this liposome was carried out ; the"Solvent-double emulsion"method was used in the preparation of gastrodine nano-sphere, the multi-indicator quality characterization to this liposome was carried out similarly. The preparation technics of liposome and nano-sphere were optimized. After a lot of experiments, the results which were described as follow:The"UV spectrophotometer"method to determination gastrodine was established. The method was validated by the HPLC. The results show that the two method no significant difference (P>0.05) under the laboratory condition.On this basis, the gastrodine's extraction technics was optimized by orthogonal. The orthogonal test show that the max rate of extraction condition was: methanol 70%, extraction time 3h, extraction temperature 70℃respectively; Under this condition extraction efficiency is 0.49%, recovery rate is 96.34%.The "Thin-film evaporation"method was used in the preparation of gastrodine nano-liposome and determinating entrapment efficiency method was constituted; The optimum prepare conditions were obtained by orthogonal experiment as follows: ratio of lecithin to cholesterol (g/g) 4: 1, ratio of PBS to organic solvent(ml/ml) 3: 1, the time of ultrasonic 60 min respectively. Validate experiment indicate that liposome mean entrapment efficiency is 60.65%, RSD is 2.31% under these conditions. Liposome have been prepared conform to the standards of pharmaceutical preparations by detecting entrapment efficiency, observing shape, stability test and so on. Its mean diameter and entrapment efficiency is 327 nm and 60.65% respectively."Solvent-double emulsion"method was used in the preparation of gastrodine-polylactide-gelatin composite nanosphere. And the technics was optimized, encapsulation efficiency and drug loading as the main indicator. Results of uniform design experiments as follows:Regarding to entrapment efficiency, optimal preparation technology: the volume ratio of oil and water is 1: 1, gelatin concentration is 3%, formaldehyde amount is 10 mL, the amount ratio of drug and material is 1: 6. Under this technology conditions, the mean entrapment efficiency is 18.02, RSD is 3.53%, and its regression equation is Y₁=80.8187-23.5317X₁+5.8281X₂-1.1745X₃+24.1829X₄Regarding to drug loading, optimal preparation technology: the volume ratio of oil and water is 1: 1, gelatin concentration is 3%, formaldehyde amount is 20 mL, the amount ratio of drug and material is 1: 2. Under this technology conditions, the mean entrapment efficiency is 74.02, RSD is 3.22%, and its regression equation is Y₂=25.7280-2.2745X₁+0.8607X₂-0.9322X₃+17.7563X₄Validate experiment indicate that the quality characterization conform to preparation demand by the way that we discuss above, micro-sphere mean diameter is 59 nm, mean entrapment efficiency is 18.02%, mean drug loading is 74.02%.